The naturally occurring diterpenoid taxol has great potential as an anti-cancer drug, and has shown activity in several tumor systems. Background information on taxol, the mechanisms of taxol's biological activity, and the synthesis of water soluble derivatives from taxol, are described in co-pending application Ser. No. 07/573,731, filed Aug. 28, 1990. All references cited herein are incorporated by reference as if reproduced in full below.
Taxol is in short supply and is relatively expensive. Further, total synthesis of taxol is quite difficult due to the bridged bicyclic portion of the taxane ring structure. Therefore, it is highly desirable to find taxol derivatives with similar biological activities, which lend themselves to easier total synthesis than taxol.
There is also a need for a method to quickly determine the biological activities of new compounds or pharmaceutical compounds having bioactivities or structures similar to taxol. The short supply and expense of taxol makes impractical the use of taxol as a standard in determining the bioactivities of other compounds; thus, it is highly desirable that a range of other standards with known biological activities be available to determine the bioactivity of taxol derivatives and other compounds relative to taxol. Useful standards should be derivatives of taxol, or the standards should be compounds which have similar structures to taxol, but which are more readily available or which can be synthesized easier than taxol. At present, some derivatives, which do not exhibit the same high biological activity as taxol, are thrown away; this waste would be eliminated by a method which uses taxol derivatives, which have significantly less biological activity than taxol, as standards in bioactivity testing, rather than utilizing more taxol, which is already in short supply and very expensive.
Thus, there is a need for taxol derivatives having a range of in vivo and in vitro activities, and there is a need for taxol derivatives or compounds having similar biological activities to taxol which are capable of easier total synthesis than taxol.